A form of environmental pollution that has attracted recent interest is light pollution, in the form of light trespass, up-light that obscures the night sky and glare or side-light that blinds at night. In addition, there is recent evidence that exposure to light at night may have detrimental effects on the health of both animals and humans. Melatonin secretion from the pineal gland has been implicated in the etiology of these adverse health effects of night light exposure.
Melatonin, N-acetyl-5-methoxytryptamine, is the principal hormone of the pineal gland, and mediates many biological functions, particularly those that are controlled by the duration of light and darkness. Melatonin is synthesized from tryptophan through serotonin, which is N-acetylated by the enzyme n-acetyl transferase or NAT, and then methylated by hydroxyindol-O-methyl transferase. The enzyme NAT is the rate-limiting enzyme for the synthesis of melatonin, and is increased by norepinephrine at the sympathetic nerve endings in the pineal gland. Norepinephrine is released at night or in the dark phase from these nerve endings. Thus, melatonin secretion is controlled mainly by light and dark phases.
The secretion of melatonin in the human is circadian, with high levels at night and low levels in the morning. The light/dark cycle is a pervasive and prominent Zeitgeber of the regulation of circadian timing system: in the presence of light, the output from the Retino-Hypothalamic Tract inhibits the melatonin synthesis, whereas darkness stimulates it.
Like myriads of circadian rhythms in mammals (drinking and feeding, wake-sleep cycle, temperature, cortisol, corticosterone etc.), the melatonin rhythm is generated by an endogenous pacemaker located in the anterior hypothalamic suprachiasmatic nuclei (SCN). In humans, the circadian rhythm for the release of melatonin is closely synchronized with the habitual hours of sleep. Typically, melatonin secretion starts at 2100 hrs (9 pm) and increases to a peak at 0200 hr (2 am) and then falls to a nadir about 0600 hr (6 am). However, a curious characteristic of the melatonin rhythm is that it can be acutely interrupted by exposure to light. It has been shown that light exposure in the early subjective night delays the timing of the circadian clock while light exposure in the late subjective night advances the timing of the clock. Exposure to light at either time suppresses melatonin secretion.
The melatonin secretion rhythm changes for shift workers, who eventually have a different rise and fall depending on their “normal” time of resting. Travelers through different time zones suffer from so-called jet lag that in most part is related to their circadian rhythm of melatonin being out of synchrony with the local clock time. Light suppression of melatonin can occur very quickly in the dark phase with secretion returning rapidly following the cessation of light. Exposure to light in the middle of the dark period results in suppression of melatonin levels of up to 85%.
All of melatonin's functions have yet to be defined, but this hormone appears to: 1) Synchronize the circadian rhythms of the body, 2) Stimulate immune function, 3) Inhibit growth of cancer cells in vitro, and 4) Reduce the progression and promotion of cancer in vivo.
Some forms of cancer, for example, certain breast cancers and prostate cancers, are hormone dependent. In the test tube, melatonin inhibits the growth of breast tumor cells, and in animals blocks the growth of breast cancer. Melatonin has recently been demonstrated to be a potent antioxidant by scavenging highly reactive hydroxyl radicals, and in vitro protects DNA from free radical damage. This effect is concentration dependent. Antioxidant activity may be one of the ways that melatonin helps to prevent cancers. In animals, removal of the pineal gland can increase the growth of some cancers. Conversely, women with profound bilateral blindness have high melatonin levels and a significantly decreased incidence of cancer of the breast, as described in Hahn R A, Profound bilateral blindness and the incidence of breast cancer, Epidemiology 1991;2:208-10.
Clinical studies have demonstrated that shift-workers who work part of, or the whole of the night, in a lighted environment may have increased rates of heart disease and cancer, as described in Kawachi I, et al., Prospective study of shift work and risk of coronary heart disease in women, Circulation 1995;92:3178-82 and Hansen J, Increased breast cancer risk among women who work predominantly at night, Epidemiology 2001;12:74-7.
Two epidemiologic studies have determined a link between exposure to light at night and an increased risk of breast cancer. In one study described in Davis S, et al., Night shift work, light at night, and risk of breast cancer, J Natl Cancer Inst 2001;93:1557-62 case patients with breast cancer (n=813), aged 20-74 years, were compared with control subjects (n=793) identified by random-digit dialing and age matched. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. The authors found that breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR=1.14 for each night per week; 95% CI=1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR=1.6; 95% CI=1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shift work (P=0.02). The results of this study provided evidence that exposure to light at night may be associated with the risk of developing breast cancer. The authors speculated that exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries.
Data from the Nurses Health Study was also analyzed to search for a link between light at night and breast cancer risk. The authors investigated the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study, described in Schernhammer E S, et al., Rotating night shifts and risk of breast cancer in women participating in the nurses' health study, J Natl Cancer Inst 2001;93:1563-8. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts of three or more days per month. From June 1988 through May 1999, 2441 incident breast cancer cases were documented. The authors observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR=1.08 [95% CI=0.99 to 1.18] and RR=1.08 [95% CI=0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR=1.36; 95% CI=1.04 to 1.78). The test for trend was statistically significant (P=0.02). They concluded that women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.
In all of the clinical studies, the adverse effect of light exposure at night on cancer risk was thought to act through suppression of melatonin levels. A recent study examined the effects of different wavelengths of light on melatonin suppression and phase shifting of the salivary melatonin rhythm in the human, described in Wright H R, and Lack L C, Effect of light wavelength on suppression and phase delay of the melatonin rhythm, Chronobiol Int 2001;18:801-8. The wavelengths compared were 660 nm (red), 595 nm (amber), 525 mn (green), 497 nm (blue/green), and 470 nm (blue) and light of each wavelength was administered using light-emitting diodes equated for irradiance of 130 muW/cm2. Fifteen volunteers participated in all five wavelength conditions and a no light control condition, with each condition conducted over two consecutive evenings. Half-hourly saliva samples were collected from 19:00 to 02:00 on night 1 and until 01:00 on night 2. Light was administered for the experimental conditions on the first night only from midnight to 02:00. Percentage melatonin suppression on night 1 and dim light melatonin onset (DLMO) for each night were calculated. The shorter wavelengths of 470, 497, and 525 nm showed the greatest melatonin suppression, 65% to 81%. The shorter wavelengths also showed the greatest DLMO delay on night 2, ranging from 27 to 36 min. There was much less suppression of melatonin by higher wavelengths, such as red or amber light.
In a rat model, exposure to light of different wavelengths also resulted in similar findings regarding melatonin suppression, as described in Honma S, et al., Light suppression of nocturnal pineal and plasma melatonin in rats depends on wavelength and time of day, Neurosci Lett 1992;147:201-4. Effects of light on pineal gland and plasma melatonin were examined in Wistar and Long-Evans rats at the 4th hour into the dark phase (light off from 18.00 h to 06.00 h) using lights of two different monochromatic wavelengths but with the same irradiance. The green light pulse (520 nm) given at 24.00 h suppressed the pineal and plasma melatonin to the day-time level for at least 2 h, while the red light (660 nm) pulse suppressed pineal melatonin only transiently and did not suppress the plasma melatonin at all.
Animal studies, in Beniashvili et al, Effect of light/dark regimen on N-nitrosoethylurea-induced transplacental carcinogenesis in rats. Cancer Lett., 2001 Feb. 10; 163(1):51-7, have shown that constant exposure to light significantly promotes transplacental carcinogenesis. Observational studies have associated night-shift work with an increased risk of breast and colorectal cancers as shown in for example Tynes et al., Incidence of breast cancer in Norweigan female radio and telegraph operators. Cancer Causes Control. 1996 Mar. 7(2):197-204; Hansen, J., Light at night, shiftwork, and breast cancer risk. J. Natl Cancer Inst. 2001 Oct. 17; 93(20):1513-5; and Schernhammer et al., Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl. Cancer Inst. 2003 Jun. 4;95(11):825-8. Furthermore, melatonin has been shown to be a free-radical scavenger and antioxidant, and conditions that involve free radical damage may be aggravated by light suppression of melatonin levels (Reiter, Potential biological consequences of excessive light exposure: melatonin suppression, DNA damage, cancer and neurodegenerative diseases. Neuroendocrinol Lett 2002 Jul. 23 Suppl 2:9-13). These findings suggest that shift-workers may have an increased danger of developing various forms of cancer due to a repetitive exposure to light at night.
Therefore, studies in humans and in rats both demonstrated that different wavelengths of light during the dark phase suppress melatonin levels differentially. White light and short wavelength light (green and blue) suppress melatonin to the greatest degree, while longer wavelengths of light (eg. red) have little or no melatonin suppression. It is therefore desirable to provide an optical filter that selectively blocks light of a wavelength capable of suppressing melatonin levels in a human that can be used by people who are exposed to melatonin suppressing light at peak melatonin production times.